Colorectal cancer

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Pathophysiology

Colorectal cancer probably arises from colorectal polyps.[1] Adenomatous polyps convert to cancers at a rate of about 1% per year.[2]

Treatment

Colorectal cancer treatment information from the National Cancer Institute's Physician Data Query


Medications

Aspirin

Aspirin may reduce mortality among patients whose tumor overexpress the enzyme cyclooxygenase 2 according to a cohort study.[3] Cyclooxygenase 2 is expressed by most colorectal cancers and is associated with reduced survival.[4]

Cetuximab

Cetuximab, an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor, may help according to a randomized controlled trial.[5]

Prognosis

5-Year Relative Survival Rates By Year Dx By Cancer Site All Ages, All Races, Both Sexes 1975-2000.

Staging information

Colorectal cancer staging information from the National Cancer Institute's Physician Data Query



Prognosis of colonic cancer[6]
Stage Five-year survival rate (%)
Stage I (T1-2N0) 93
Stage IIA (T3N0) 85
Stage IIB (T4N0) 72
Stage IIIA (T1-2 N1) 83
Stage IIIB (T3-4 N1) 64
Stage IIIC (N2) 44
Stage IV 8

Screening

For more information, see: colonic polyp.


In the United States, both underuse and overuse of screening occur.[7]

Allowing patients to choose their method of screening might be the most effective.[8]

Practice guidelines

While clinical practice guidelines are available to address screening, gastroenterologists may not follow the guidelines well.[9]

US Preventive Services Task Force

A clinical practice guideline by the US Preventive Services Task Force has addressed colorectal cancer:[10]

  • "recommends screening for colorectal cancer using fecal occult blood testing, sigmoidoscopy, or colonoscopy in adults, beginning at age 50 years and continuing until age 75 years."
  • "recommends against routine screening for colorectal cancer in adults 76 to 85 years of age. There may be considerations that support colorectal cancer screening in an individual patient."
  • "recommends against screening for colorectal cancer in adults older than age 85 years"
  • "the evidence is insufficient to assess the benefits and harms of computed tomographic colonography and fecal DNA testing (a subsequent study found that DNA was more sensitive but less specific[11])"

American College of Gastroenterology

Clinical practice guideline published in 2009 by the American College of Gastroenterology recommends:[12]

  • "Cancer prevention tests should be offered fi rst. The preferred CRC prevention test is colonoscopy every 10 years, beginning at age 50. (Grade 1 B) Screening should begin at age 45 years in African Americans (Grade 2 C)"
  • "Cancer detection test. This test should be offered to patients who decline colonoscopy or another cancer prevention test. The preferred cancer detection test is annual FIT for blood (Grade 1 B)"

Notes: Grade 2C recommendation reflects "2C/Weak recommendation, low-quality or very low-quality evidence"

The AGA has also issued guidance on surveillance after colonoscopy.[13]

American College of Physicians

The American College of Physicians has issued guidelines.Screening for Colorectal Cancer: A Guidance Statement From the American College of Physicians 2012

American Cancer Society

For screening, a clinical practice guideline jointly published in 2007 by the American Cancer Society and other groups recommends one of:[14]

  • Flexible sigmoidoscopy every 5 years
  • Barium enema every 5 years
  • Virtual colonography (a noninvasive test based on computed tomography) every 5 years
  • Colonoscopy every 10 years

When polyps are found, a clinical practice guideline jointly published in 2006 by the American Cancer Society and other groups states:[15]

  • High risk polyps are 1) 3 or more synchronous adenomas, 2) adenomas ≥1 cm in diameter, or 3) villus histology or high-grade dysplasia.
  • High risk polyps should have follow-up colonoscopy in 3 years
  • Low risk polyps should have repeat colonoscopy in 5 to 10 years
  • If no adenomas are found, follow-up evaluation should be at 10 years

Evidence

A cost-benefit analysis[16] and a meta-analysis[17] have reviewed studies of fecal testing and colonic imaging. Immunochemical fecal occult blood (I-FOBT) tests may be the most effective.[16][18][19]

A validation of guidelines found:[20]

  • High risk adenomas - 9% of an advanced adenoma at 4 years of follow-up.
  • Low risk adenomas - 5% of an advanced adenoma at 4 years of follow-up.

Fecal testing

Feces can be tested for occult blood by either:

  • Chemical reaction with guaiac
  • Immumohistochemistry test for components of blood such as hemoglobin or haptoglobin. With this method, approximatelly 8% of patients will be positive after three years of yearly testing and 40% of those positive will be found to have eitehr advanced adenoma or cancer.[21] The method may be the most effective[16][18][19] and also may be improved if patients are taking low dose aspirin to prevent vascular disease.[22] In a randomized controlled trial, immunochemical testing, as compared to colonoscopy, found a similar number of colorectal cancers but less adenomas.[23] Immumohistochemistry testing may not have to be repeated annualy as needed by guaiac-based testing.[24]
  • DNA DNA testing more be more sensitive than fecal immunochemical testing.[25]

Visualization

Selected studies of the benefit of colorectal cancer screening[26][27] [28][29][30][31][32][33][34][35]
Procedure Study Benefit Number needed to screen
(For observational studies, assuming control rate of 1%)
Fecal occult blood annually Minnesota Colon Cancer Control Study[29]
Randomized controlled trial
46,551 patients for 13 years
Colorectal cancer death:
Relative risk ratio 0.67
Relative risk reduction 33%
305
Double-contrast barium enema Ontario Cancer Registry[30]
Cohort study
13,849 patients who had a DCBE 36 months prior to the diagnosis of CRC
Colorectal cancer incidence:
False negative rate (1-Sensitivity) 22%
Sensitivity 78%
142
Sigmoidoscopy PLCO trial[26]
Sigmoidoscopy screening with one repeat at 3-5 years
Randomized controlled trial
154,900 for 12 years
Colorectal cancer death:
Relative risk ratio 0.74 (sig)
1025
SCORE trial[27]
Sigmoidoscopy one time
Randomized controlled trial
34,272 subjects for 10 years
Colorectal cancer death:
Relative risk ratio 0.78 (insig)
1000
UK Flexible Sigmoidoscopy Trial Investigators.[28]
Sigmoidoscopy one time
Randomized controlled trial
170,000 subjects for 11 years
Colorectal cancer death:
Relative risk ratio 0.67 (95% CI: 0.60-0.76)
688
Kaiser Permanente[32]
Case-control study
261 case patients and 868 control patients for 10 years
Colorectal cancer death:
Odds ratio 0.41
170
Telemark Polyp Study I[33]
Cohort study
400 case patients and 399 controls for 7 to 11 years
Colorectal cancer incidence:
Relative risk ratio 0.2
Relative risk reduction 80%
125
Colonoscopy National Polyp Study[34]
Cohort study
1418 patients for 5.8 years
Colorectal cancer incidence:
Relative risk ratio 0.1
Relative risk reduction 90%
111
Ontario Cancer Registry[35]
Case-control study
10,292 case patients and 51,460 controls for 7.8 years
Colorectal cancer death:
Odds ratio 0.69
325

Visualization may be less effective in the right colon.[36][35]

Capsule endoscopy

Capsule endoscopy is less accurate than optical endoscopy.[37]

Computed tomographic colonography

Laxative-free "computed tomographic colonography was accurate in detecting adenomas 10 mm or larger but less so for smaller lesions." [38]

Prevention

Aspirin chemoprophylaxis

A clinical practice guideline by the U.S. Preventive Services Task Force (USPSTF) recommended against taking aspirin (grade D recommendation).[39] The Task Force acknowledged that aspirin may reduce the incidence of colorectal cancer, but "concluded that harms outweigh the benefits of aspirin and NSAID use for the prevention of colorectal cancer". Long-term doses over 81 mg per day may increase bleeding events.[40]

Subsequent meta-analyses conclude:

  • "300 mg or more of aspirin a day for about 5 years is effective in primary prevention of colorectal cancer in randomised controlled trials, with a latency of about 10 years".[41]
  • "Aspirin is effective for the prevention of colorectal adenomas in individuals with a history of these lesions."[42] The number needed to treat was about 33.

Aspirin and celecoxib may help individuals with an increased risk of CRC according to the NIHR Health Technology Assessment programme (UK).[43]

Calcium

A meta-analysis by the Cochrane Collaboration of randomized controlled trials published through 2002 concluded "Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps, this does not constitute sufficient evidence to recommend the general use of calcium supplements to prevent colorectal cancer.".[44] Subsequently, one randomized controlled trial by the Women's Health Initiative (WHI) reported negative results.[45] A second randomized controlled trial reported reduction in all cancers, but had insufficient colorectal cancers for analysis.[46]

References

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